Prediction of cytochrome P450 mediated metabolism

Lars Olsen; Chris Oostenbrink; Flemming Steen Jørgensen

doi:10.1016/j.addr.2015.04.020

Prediction of cytochrome P450 mediated metabolism

Lars Olsen, Chris Oostenbrink, Flemming Steen Jørgensen

62 Citations (Scopus)

Abstract

Cytochrome P450 enzymes (CYPs) form one of the most important enzyme families involved in the metabolism of xenobiotics. CYPs comprise many isoforms, which catalyze a wide variety of reactions, and potentially, a large number of different metabolites can be formed. However, it is often hard to rationalize what metabolites these enzymes generate. In recent years, many different in silico approaches have been developed to predict binding or regioselective product formation for the different CYP isoforms. These comprise ligand-based methods that are trained on experimental CYP data and structure-based methods that consider how the substrate is oriented in the active site or/and how reactive the part of the substrate that is accessible to the heme group is. We will review key aspects for various approaches that are available to predict binding and site of metabolism (SOM), what outcome can be expected from the predictions, and how they could potentially be improved.

Original language	English
Journal	Advanced Drug Delivery Reviews
Volume	86
Pages (from-to)	61-71
Number of pages	11
ISSN	0169-409X
DOIs	https://doi.org/10.1016/j.addr.2015.04.020
Publication status	Published - 23 Jun 2015

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title = "Prediction of cytochrome P450 mediated metabolism",

abstract = "Cytochrome P450 enzymes (CYPs) form one of the most important enzyme families involved in the metabolism of xenobiotics. CYPs comprise many isoforms, which catalyze a wide variety of reactions, and potentially, a large number of different metabolites can be formed. However, it is often hard to rationalize what metabolites these enzymes generate. In recent years, many different in silico approaches have been developed to predict binding or regioselective product formation for the different CYP isoforms. These comprise ligand-based methods that are trained on experimental CYP data and structure-based methods that consider how the substrate is oriented in the active site or/and how reactive the part of the substrate that is accessible to the heme group is. We will review key aspects for various approaches that are available to predict binding and site of metabolism (SOM), what outcome can be expected from the predictions, and how they could potentially be improved.",

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T1 - Prediction of cytochrome P450 mediated metabolism

AU - Olsen, Lars

AU - Oostenbrink, Chris

AU - Jørgensen, Flemming Steen

PY - 2015/6/23

Y1 - 2015/6/23

N2 - Cytochrome P450 enzymes (CYPs) form one of the most important enzyme families involved in the metabolism of xenobiotics. CYPs comprise many isoforms, which catalyze a wide variety of reactions, and potentially, a large number of different metabolites can be formed. However, it is often hard to rationalize what metabolites these enzymes generate. In recent years, many different in silico approaches have been developed to predict binding or regioselective product formation for the different CYP isoforms. These comprise ligand-based methods that are trained on experimental CYP data and structure-based methods that consider how the substrate is oriented in the active site or/and how reactive the part of the substrate that is accessible to the heme group is. We will review key aspects for various approaches that are available to predict binding and site of metabolism (SOM), what outcome can be expected from the predictions, and how they could potentially be improved.

AB - Cytochrome P450 enzymes (CYPs) form one of the most important enzyme families involved in the metabolism of xenobiotics. CYPs comprise many isoforms, which catalyze a wide variety of reactions, and potentially, a large number of different metabolites can be formed. However, it is often hard to rationalize what metabolites these enzymes generate. In recent years, many different in silico approaches have been developed to predict binding or regioselective product formation for the different CYP isoforms. These comprise ligand-based methods that are trained on experimental CYP data and structure-based methods that consider how the substrate is oriented in the active site or/and how reactive the part of the substrate that is accessible to the heme group is. We will review key aspects for various approaches that are available to predict binding and site of metabolism (SOM), what outcome can be expected from the predictions, and how they could potentially be improved.

U2 - 10.1016/j.addr.2015.04.020

DO - 10.1016/j.addr.2015.04.020

M3 - Journal article

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SN - 0169-409X

VL - 86

SP - 61

EP - 71

JO - Advanced Drug Delivery Reviews

JF - Advanced Drug Delivery Reviews

ER -

Prediction of cytochrome P450 mediated metabolism

Abstract

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